Publications by authors named "Denisa Margină"

39 Publications

The Radioprotective Effect of Procaine and Procaine-Derived Product Gerovital H3 in Lymphocytes from Young and Aged Individuals.

Oxid Med Cell Longev 2020 24;2020:3580934. Epub 2020 Jun 24.

Department of Biology, Molecular Toxicology Group, University of Konstanz, D-78457 Konstanz, Germany.

Ionizing radiation induces genomic instability in living organisms, and several studies reported an ageing-dependent radiosensitivity. Chemical compounds, such as scavengers, radioprotectors, and modifiers, contribute to reducing the radiation-associated toxicity. These compounds are often antioxidants, and therefore, in order to be effective, they must be present before or during exposure to radiation. However, not all antioxidants provide radioprotection. In this study, we investigated the effects of procaine and of a procaine-based product Gerovital H3 (GH3) on the formation of endogenous and X-ray-induced DNA strand breaks in peripheral blood mononuclear cells (PBMCs) isolated from young and elderly individuals. Interestingly, GH3 showed the strongest radioprotective effects in PBMCs from young subjects, while procaine reduced the endogenous amount of DNA strand breaks more pronounced in aged individuals. Both procaine and GH3 inhibited lipid peroxidation, but procaine was more effective in inhibiting mitochondria free radicals' generation, while GH3 showed a higher antioxidant action on macrophage-induced low-density lipoprotein oxidation. Our findings provide new insights into the mechanisms underlying the distinct effects of procaine and GH3 on DNA damage.
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http://dx.doi.org/10.1155/2020/3580934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334788PMC
June 2020

Analysis of the intricate effects of polyunsaturated fatty acids and polyphenols on inflammatory pathways in health and disease.

Food Chem Toxicol 2020 Sep 5;143:111558. Epub 2020 Jul 5.

Laboratory of Toxicology and Forensic Sciences, Medical School, University of Crete, 71003, Heraklion, Greece; Department of Analytical and Forensic Medical Toxicology, Sechenov University, 2-4 Bolshaya Pirogovskaya st, 119991, Moscow, Russia. Electronic address:

Prevention and treatment of non-communicable diseases (NCDs), including cardiovascular disease, diabetes, obesity, cancer, Alzheimer's and Parkinson's disease, arthritis, non-alcoholic fatty liver disease and various infectious diseases; lately most notably COVID-19 have been in the front line of research worldwide. Although targeting different organs, these pathologies have common biochemical impairments - redox disparity and, prominently, dysregulation of the inflammatory pathways. Research data have shown that diet components like polyphenols, poly-unsaturated fatty acids (PUFAs), fibres as well as lifestyle (fasting, physical exercise) are important factors influencing signalling pathways with a significant potential to improve metabolic homeostasis and immune cells' functions. In the present manuscript we have reviewed scientific data from recent publications regarding the beneficial cellular and molecular effects induced by dietary plant products, mainly polyphenolic compounds and PUFAs, and summarize the clinical outcomes expected from these types of interventions, in a search for effective long-term approaches to improve the immune system response.
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http://dx.doi.org/10.1016/j.fct.2020.111558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335494PMC
September 2020

Chronic Inflammation in the Context of Everyday Life: Dietary Changes as Mitigating Factors.

Int J Environ Res Public Health 2020 06 10;17(11). Epub 2020 Jun 10.

Department Forensic Sciences and Toxicology, University of Crete, Faculty of Medicine, 71003 Heraklion, Greece.

The lifestyle adopted by most people in Western societies has an important impact on the propensity to metabolic disorders (e.g., diabetes, cancer, cardiovascular disease, neurodegenerative diseases). This is often accompanied by chronic low-grade inflammation, driven by the activation of various molecular pathways such as STAT3 (signal transducer and activator of transcription 3), IKK (IκB kinase), MMP9 (matrix metallopeptidase 9), MAPK (mitogen-activated protein kinases), COX2 (cyclooxigenase 2), and NF-Kβ (nuclear factor kappa-light-chain-enhancer of activated B cells). Multiple intervention studies have demonstrated that lifestyle changes can lead to reduced inflammation and improved health. This can be linked to the concept of real-life risk simulation, since humans are continuously exposed to dietary factors in small doses and complex combinations (e.g., polyphenols, fibers, polyunsaturated fatty acids, etc.). Inflammation biomarkers improve in patients who consume a certain amount of fiber per day; some even losing weight. Fasting in combination with calorie restriction modulates molecular mechanisms such as m-TOR, FOXO, NRF2, AMPK, and sirtuins, ultimately leads to significantly reduced inflammatory marker levels, as well as improved metabolic markers. Moving toward healthier dietary habits at the individual level and in publicly-funded institutions, such as schools or hospitals, could help improving public health, reducing healthcare costs and improving community resilience to epidemics (such as COVID-19), which predominantly affects individuals with metabolic diseases.
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http://dx.doi.org/10.3390/ijerph17114135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312944PMC
June 2020

Obesity ‑ a risk factor for increased COVID‑19 prevalence, severity and lethality (Review).

Mol Med Rep 2020 Jul 5;22(1):9-19. Epub 2020 May 5.

Laboratory of Toxicology, Medical School, University of Crete, 71409 Heraklion, Greece.

Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are a group of viruses that cause infections in the human respiratory tract, which can be characterized clinically from mild to fatal. The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is the virus responsible. The global spread of COVID‑19 can be described as the worst pandemic in humanity in the last century. To date, COVID‑19 has infected more than 3,000,000 people worldwide and killed more than 200,000 people. All age groups can be infected from the virus, but more serious symptoms that can possibly result in death are observed in older people and those with underlying medical conditions such as cardiovascular and pulmonary disease. Novel data report more severe symptoms and even a negative prognosis for the obese patients. A growing body of evidence connects obesity with COVID‑19 and a number of mechanisms from immune system activity attenuation to chronic inflammation are implicated. Lipid peroxidation creates reactive lipid aldehydes which in a patient with metabolic disorder and COVID‑19 will affect its prognosis. Finally, pregnancy‑associated obesity needs to be studied further in connection to COVID‑19 as this infection could pose high risk both to pregnant women and the fetus.
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http://dx.doi.org/10.3892/mmr.2020.11127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248467PMC
July 2020

Overview of the effects of chemical mixtures with endocrine disrupting activity in the context of real-life risk simulation: An integrative approach (Review).

World Acad Sci J 2019 Jul 5;1(4):157-164. Epub 2019 Aug 5.

Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71409 Heraklion.

Research over the past years has indicated that chronic human exposure to very low doses of various chemical species in mixtures and administered via different routes (percutaneous, orally, etc.) should be the main focus of new biochemical and toxicological studies. Humans have daily contact with various chemicals, such as food additives, pesticides from fruits/vegetables, antibiotics (and other veterinary drugs) from meat, different types of preservatives from cosmetics, to name a few. Simultaneous exposure to this wide array of chemicals does not produce immediate effects, but summative effect/s over time that may be clinically manifested several years thereafter. Classical animal studies designed to test the toxic outcome of a single chemical are not suitable to assess, and then extrapolate to humans, the effects of a whole mixture of chemicals. Testing the aftermath of a combination of chemicals, at low doses, around or below the no observed adverse effect is stressed by many toxicologists. Thus, there is a need to reformulate the design of biochemical and toxicological studies in order to perform real-life risk simulation. This review discuss the potential use of computational methods as a complementary tool for and toxicity tests with a high predictive potential that could contribute to reduce animal testing, cost and time, when assessing the effects of chemical combinations. This review focused on the use of these methods to predict the potential endocrine disrupting activity of a mixture of chemicals.
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http://dx.doi.org/10.3892/wasj.2019.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188405PMC
July 2019

A review of the alleged health hazards of monosodium glutamate.

Compr Rev Food Sci Food Saf 2019 Jul 8;18(4):1111-1134. Epub 2019 May 8.

Faculty of Pharmacy, "Carol Davila" Univ. of Medicine and Pharmacy, Traian Vuia 6, Bucharest, 020956, Romania.

Monosodium glutamate (MSG) is an umami substance widely used as flavor enhancer. Although it is generally recognized as being safe by food safety regulatory agencies, several studies have questioned its long-term safety. The purpose of this review was to survey the available literature on preclinical studies and clinical trials regarding the alleged adverse effects of MSG. Here, we aim to provide a comprehensive overview of the reported possible risks that may potentially arise following chronic exposure. Furthermore, we intend to critically evaluate the relevance of this data for dietary human intake. Preclinical studies have associated MSG administration with cardiotoxicity, hepatotoxicity, neurotoxicity, low-grade inflammation, metabolic disarray and premalignant alterations, along with behavioral changes. Moreover, links between MSG consumption and tumorigenesis, increased oxidative stress and apoptosis in thymocytes, as well as genotoxic effects in lymphocytes have been reported. However, in reviewing the available literature, we detected several methodological flaws, which led us to conclude that these studies have limited relevance for extrapolation to dietary human intakes of MSG risk exposure. Clinical trials have focused mainly on the effects of MSG on food intake and energy expenditure. Besides its well-known impact on food palatability, MSG enhances salivary secretion and interferes with carbohydrate metabolism, while the impact on satiety and post-meal recovery of hunger varied in relation to meal composition. Reports on MSG hypersensitivity, also known as 'Chinese restaurant syndrome', or links of its use to increased pain sensitivity and atopic dermatitis were found to have little supporting evidence. Based on the available literature, we conclude that further clinical and epidemiological studies are needed, with an appropriate design, accounting for both added and naturally occurring dietary MSG. Critical analysis of existing literature, establishes that many of the reported negative health effects of MSG have little relevance for chronic human exposure and are poorly informative as they are based on excessive dosing that does not meet with levels normally consumed in food products.
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http://dx.doi.org/10.1111/1541-4337.12448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952072PMC
July 2019

HIV‑1 integrase inhibitors targeting various DDE transposases: Retroviral integration versus RAG‑mediated recombination (Review).

Mol Med Rep 2019 Dec 30;20(6):4749-4762. Epub 2019 Oct 30.

Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 020956 Bucharest, Romania.

Transposases are ubiquitous mobile genetic elements responsible for genome development, driving rearrangements, such as insertions, deletions and translocations. Across species evolution, some transposases are tamed by their host and are made part of complex cellular systems. The proliferation of retroviruses is also dependent on transposase related enzymes termed integrases. Recombination‑activating gene protein (RAG)1 and metnase are just two examples of transposase domestication and together with retroviral integrases (INs), they belong to the DDE polynucleotidyl transferases superfamily. They share mechanistic and structural features linked to the RNase H‑like fold, harboring a DDE(D) metal dependent catalytic motif. Recent antiretroviral compounds target the catalytic domain of integrase, but they also have the potential of inhibiting other related enzymes. In this review, we report the activity of different classes of integrase inhibitors on various DDE transposases. Computational simulations are useful to predict the extent of off‑target activity and have been employed to study the interactions between RAG1 recombinase and compounds from three different pharmacologic classes. We demonstrate that strand‑transfer inhibitors display a higher affinity towards the RAG1 RNase H domain, as suggested by experimental data compared to allosteric inhibitors. While interference with RAG1 and 2 recombination is associated with a negative impact on immune function, the inhibition of metnase or HTLV‑1 integrase opens the way for the development of novel therapies for refractory cancers.
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http://dx.doi.org/10.3892/mmr.2019.10777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854553PMC
December 2019

Preclinical and clinical results regarding the effects of a plant-based antidiabetic formulation versus well established antidiabetic molecules.

Pharmacol Res 2019 12 4;150:104522. Epub 2019 Nov 4.

"N. Paulescu" National Institute of Diabetes, Nutrition and Metabolic Diseases, Ion Movilă 5-7, Bucharest, 030167, Romania; "Carol Davila" University of Medicine and Pharmacy, Faculty of Dentistry, Department of Department of Endocrinology, Calea Plevnei 17-23, Bucharest, 020021, Romania.

Diabetes mellitus (DM) is a complex syndrome with debilitating long-term complications, comprising alterations of carbohydrate, protein and lipid metabolisms, along increased oxidative stress and chronic low-grade inflammation. Diet management and plant-based formulations can improve the metabolic status of patients, being used as adjuvants of classic antidiabetic therapy. The purpose of our study was to evaluate the impact of a plant-based antidiabetic formulation (PBAF), containing Vaccinium myrtillus, Ribes nigrum, Rosa canina and Capsicum annuum, on the increased oxidative burden found in diabetes mellitus, comparing it with the effects of metformin and gliclazide. Firstly, we characterized the individual plant-derived components of this formulation and also assessed their in vitro radical scavenging capacity. We devised a preclinical study protocol to examine the impact of the PBAF, along metformin and gliclazide, on tissue histology as well as on the redox status of tissue, mitochondria, serum and serum lipoproteins of alloxan-induced diabetic Wistar rats. Subsequently, we assessed their long-term impact on the redox status of serum and isolated serum lipoproteins of type 2 DM (T2DM) patients, taking into consideration their cardiometabolic profile. In the preclinical stage, we found that PBAF was able to enhance total serum antioxidant defense, while metformin yielded the best results regarding the advanced glycation and protein/lipid oxidation of serum and of serum lipoproteins. The latter also improved overall serum redox status and HDL redox function. Also, antidiabetic treatment seemed to increase mitochondrial redox activity, without overturning overall tissue redox balance. Histologically, liver and brain tissues of treated diabetic rats were fairly similar to those of non-diabetic rats. In T2DM patients, the most striking results involved the effects on serum lipoproteins. The tested PBAF exerted protective antioxidant effects on low-density and, especially, on high density lipoproteins. We conclude that this formulation might constitute a good addition to the well-established pharmacological approach of DM, contributing to the reduction of overall oxidative burden.
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http://dx.doi.org/10.1016/j.phrs.2019.104522DOI Listing
December 2019

Discovery of natural naphthoquinones as sortase A inhibitors and potential anti-infective solutions against Staphylococcus aureus.

Drug Dev Res 2019 12 4;80(8):1136-1145. Epub 2019 Sep 4.

Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

Three natural naphthoquinones were screened to find new anti-virulence agents as inhibitors against sortase A from Staphylococcus aureus (SaSrtA) by quantifying the increase in fluorescence intensity upon substrate cleavage at various concentrations. The 5-hydroxy-1,4-naphthalenedione derivatives, juglone and plumbagin, demonstrated a potent inhibitory effect, with IC values of 1.78 μM, respectively, 16.71 μM. The related 2-hydroxy-1,4-naphthalenedione derivative, lawsone, demonstrated the selectivity of the chemical scaffold having no significant effect on SaSrtA. The experimental assay was reinforced by molecular docking experiments, antimicrobial, and toxicological studies. Molecular docking studies and the electrophilic character analysis suggest bonding to the enzyme active cysteine residue by a Michael addition reaction. None of the compounds had a significant effect on the concentration of total thiol proteins in the Daphnia magna toxicological assay after 24 hr exposure. Juglone and plumbagin moderately inhibited biofilm formation with no significant effect on bacterial growth of S. aureus, Enterococcus faecalis, and Staphylococcus epidermidis, indicating a selective anti-virulence profile.
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http://dx.doi.org/10.1002/ddr.21599DOI Listing
December 2019

Predictive power of the Triticum root elongation test for the assessment of novel anti‑proliferative therapies.

Int J Mol Med 2019 Jul 10;44(1):16-24. Epub 2019 May 10.

Faculty of Pharmacy, 'Carol Davila' University of Medicine and Pharmacy, 020956 Bucharest, Romania.

The use of alternative techniques to reduce the number of animals used in anticancer research is an issue of current interest. The aim of this study was to validate the use of a simple and efficient alternative tool for the assessment of the potential of novel anti‑proliferative agents. A set of 20 compounds with various mechanisms were tested in the Triticum aestivum root elongation assay, using aminophylline as negative control. Hierarchical cluster analyses were performed using the furthest neighbor method based on Euclidean distance measure, and the compounds were statistically analyzed in reference to their anti‑proliferative pattern registered in the NCI60 human tumor cell line anticancer drug screen. A correlation between the Triticum test results and the NCI60 anti‑proliferative profile was made for a number of human cells that we defined as the Triticum cell panel. Linear equations were computed that can be used to transform the inhibitory effect measured in any future Triticum assay in order to predict the effect on particular human cells. Of the tested anti‑proliferative agents, methotrexate, colchicine, cantharidin, cisplatin and verapamil produced a growth inhibition over 50%. On the whole, the findings of this study suggest that the Triticum test can be used to detect several types of anti‑proliferative mechanisms, particularly those targeting tubulin, rendering it a useful tool with which to identify novel mitotic spindle inhibitors.
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http://dx.doi.org/10.3892/ijmm.2019.4192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559296PMC
July 2019

Neuroprotective effects of Scrophularia buergeriana extract against glutamate-induced toxicity in SH-SY5Y cells.

Int J Mol Med 2019 May 19;43(5):2144-2152. Epub 2019 Mar 19.

Department of Analytical and Forensic Medical Toxicology, Sechenov University, Moscow 119991, Russia.

The aim of this study was to investigate the antioxidant and anti‑apoptotic activities, as well as the underlying mechanisms of action, of Scrophularia buergeriana (S. buergeriana) extract (SBE) in glutamate‑induced SH‑SY5Y cell death. The roots of S. buergeriana were extracted with 70% ethanol, and standardized SBE was used in this study. To induce cytotoxicity, the SH‑SY5Y cells were exposed to glutamate for 3 h, or pre‑treated with SBE for 1 h, and subsequently incubated with glutamate for 3 h. The neuroprotective effects were assessed by measuring cell viability and the total glutathione contents using commercial kits. The antioxidant and anti‑apoptotic mechanisms of action of SBE were evaluated by western blot analysis. The results confirmed that glutamate‑induced toxicity was caused by reactive oxygen species (ROS) production, leading to oxidative stress and DNA damage, thus leading to cell death. However, treatment of the SH‑SY5Y cells with SBE significantly increased the viability of the cells exposed to glutamate by upregulating the levels of antioxidant proteins, such as superoxide dismutase (SOD)1, SOD2 and glutathione peroxidase‑1 (GPx‑1), and directly enhancing the total glutathione contents. Furthermore, SBE attenuated DNA impairment and decreased B‑cell lymphoma-2 (Bcl‑2)‑associated X protein (Bax), cleaved caspase‑3 and cleaved poly(adenosine diphosphate (ADP)‑ribose) polymerase (PARP) activation. In addition, SBE upregulated Bcl‑2 expression via p38 mitogen‑activated protein kinases (MAPKs). On the whole, the findings of this study demonstrated that SBE exerts neuroprotective effects against glutamate‑induced cell toxicity through its antioxidant and anti‑apoptotic activities.
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http://dx.doi.org/10.3892/ijmm.2019.4139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443351PMC
May 2019

Spectrophotometric versus spectrofluorometric assessment in the study of the relationships between lipid peroxidation and metabolic dysregulation.

Chem Biol Drug Des 2019 06 30;93(6):1026-1035. Epub 2019 Jan 30.

"N. Paulescu" National Institute of Diabetes, Nutrition and Metabolic Diseases Bucharest, Bucharest, Romania.

Reactive oxygen species are crucial to normal cell function, but are also part of the pathogenesis of multiple modern maladies. As such, sensitive, fast, and reliable methods of appreciating redox status are needed. We aimed to optimize the Amplex Red (AR) and ferric-xylenol orange (FOX) methods using human serum samples, rat tissue homogenates, and mitochondrial preparations. For AR, we intended to reduce probe concentration, maintaining method sensitivity, as well as extending its use from isolated lipoproteins samples, and readjust it for a high-throughput application. Also, we evaluated the usefulness of a modified xylenol orange-based spectrophotometric protocol, comparing and contrasting these methods in terms of clinical relevance and suitability for their further use in assessing redox status of various biological samples in different pathological conditions. Our results show that these optimized protocols are suitable for complex in vivo studies, as they require low quantities of sample and reagents, and are sensitive, rapid, and economical, with the option of adapting them for high-throughput analysis. For a better assessment of oxidative status of serum-derived samples, the two methods can be used concurrently, while for tissue-derived ones, either can be employed for the measurement of a global redox status.
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http://dx.doi.org/10.1111/cbdd.13474DOI Listing
June 2019

The Akt pathway in oncology therapy and beyond (Review).

Int J Oncol 2018 Dec 16;53(6):2319-2331. Epub 2018 Oct 16.

Faculty of Pharmacy, 'Carol Davila' University of Medicine and Pharmacy, 020956 Bucharest, Romania.

Protein kinase B (Akt), similar to many other protein kinases, is at the crossroads of cell death and survival, playing a pivotal role in multiple interconnected cell signaling mechanisms implicated in cell metabolism, growth and division, apoptosis suppression and angiogenesis. Akt protein kinase displays important metabolic effects, among which are glucose uptake in muscle and fat cells or the suppression of neuronal cell death. Disruptions in the Akt‑regulated pathways are associated with cancer, diabetes, cardiovascular and neurological diseases. The regulation of the Akt signaling pathway renders Akt a valuable therapeutic target. The discovery process of Akt inhibitors using various strategies has led to the identification of inhibitors with great selectivity, low side‑effects and toxicity. The usefulness of Akt emerges beyond cancer therapy and extends to other major diseases, such as diabetes, heart diseases, or neurodegeneration. This review presents key features of Akt structure and functions, and presents the progress of Akt inhibitors in regards to drug development, and their preclinical and clinical activity in regards to therapeutic efficacy and safety for patients.
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http://dx.doi.org/10.3892/ijo.2018.4597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203150PMC
December 2018

Toxicity of plant extracts containing pyrrolizidine alkaloids using alternative invertebrate models.

Mol Med Rep 2018 Jun 26;17(6):7757-7763. Epub 2018 Mar 26.

Faculty of Pharmacy, University of Medicine and Pharmacy 'Carol Davila', 020956 Bucharest, Romania.

Pyrrolizidine alkaloids (PAs) are a widespread class of hepatotoxic heterocyclic organic compounds found in approximately 3% of world flora. Some PAs have been shown to have genotoxic and carcinogenic effects. The present study focuses on the toxicity effects of four dry extracts obtained from medicinal plants (Senecio vernalis, Symphytum officinale, Petasites hybridus and Tussilago farfara), on two aquatic organisms, Artemia salina and Daphnia magna, and the correlation with their PAs content. A new GC‑MS method, using a retention time (TR)‑5MS type capillary column was developed. PAs Kovats retention indices, for this type of column were computed for the first time. The lethal dose 50% (LC50) values for the two invertebrate models were correlated (Pearson 's coefficient, >0.9) and the toxicity was PA concentration-dependent, for three of the four extracts. All tested extracts were found to be toxic in both aquatic organism models. The results can be used to develop a GC‑MS validated method for the assay of PAs in medicinal plants with a further potential application in the risk assessment study of PAs toxicity in humans.
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http://dx.doi.org/10.3892/mmr.2018.8795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983973PMC
June 2018

Insulin-Leptin Axis, Cardiometabolic Risk and Oxidative Stress in Elderly with Metabolic Syndrome.

Exp Clin Endocrinol Diabetes 2018 02 8. Epub 2018 Feb 8.

Liquid Genomics, Inc., Torrance, CA; University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California, USA.

Insulin and leptin have an overlapping anorexigenic action as well as opposite effects on glucose and lipid metabolism. The study focuses on the biochemical and clinical relevance of new indices of insulin-leptin axis utilized in the study of the relationships between leptinemia, insulin sensitivity and oxidative stress, in elderly subjects with metabolic syndrome. We conducted clinical studies on elderly people with metabolic syndrome versus control subjects by creating new insulin-adipogenic indices, namely Insulin-to-Leptin Ratio (ILR) and Insulin-Adipogenic Resistance index (IAR-index). Inflammation and oxidative stress biomarkers evaluated were the high-sensitivity C-reactive protein (hsCRP), the advanced oxidation protein products (AOPP), and the serum antioxidant capacity measured as ferric reducing antioxidant potential (FRAP). The metabolic syndrome group showed significantly (p<0.01) lower levels of ILR and not significant (p=0.09) higher values of IAR-index, as compared to the control group. In metabolic syndrome subjects, the IAR-index was significantly positively correlated with uric acid (r=0.313, p<0.05), FRAP (r=0.347, p<0.05) and AOPP (r=0.677, p<0.01), and negatively correlated with HDL-cholesterol (r=- 0.340, p<0.05) as well as with the ratio FRAP/uric acid (r=- 0.315, p<0.05). ILR and IAR-index reflected the biological state of adipose and pancreatic β-cells and seem to depict the adipo-insular axis status related to metabolic and oxidative stress better than individual markers. Therefore, ILR and IAR-index could represent integrated high-potential biomarkers for disease and patient stratification.
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http://dx.doi.org/10.1055/s-0043-123825DOI Listing
February 2018

Molecular Docking and Screening Studies of New Natural Sortase A Inhibitors.

Int J Mol Sci 2017 Oct 23;18(10). Epub 2017 Oct 23.

Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania.

To date, multi-drug resistant bacteria represent an increasing health threat, with a high impact on mortality, morbidity, and health costs on a global scale. The ability of bacteria to rapidly and permanently acquire new virulence factors and drug-resistance elements requires the development of new antimicrobial agents and selection of new proper targets, such as sortase A. This specific bacterial target plays an important role in the virulence of many Gram-positive pathogens, and its inhibition should produce a mild evolutionary pressure which will not favor the development of resistance. A primary screening using a fluorescence resonance energy transfer assay was used to experimentally evaluate the inhibitory activity of several compounds on sortase A. Using molecular docking and structure-activity relationship analyses, several lead inhibitors were identified, which were further tested for antimicrobial activity using the well diffusion test and minimum inhibitory concentration. The toxicity was assessed using the test and used as a future screening filter. Three natural compounds were identified in this study as promising candidates for further development into therapeutically useful anti-infective agents that could be used to treat infections caused by multi-drug resistant bacterial pathogens which include sortase A in their enzymatic set.
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http://dx.doi.org/10.3390/ijms18102217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666896PMC
October 2017

Current evidence on the effect of dietary polyphenols intake on chronic diseases.

Food Chem Toxicol 2017 Dec 14;110:286-299. Epub 2017 Oct 14.

Biomedical, Odontoiatric, Morphological and Functional Images Department, Occupational Medicine Section, University of Messina, Messina 98125, Italy. Electronic address:

Polyphenols are secondary metabolites of plants. They comprise several antioxidant compounds and they are generally considered to be involved in the defense against human chronic diseases. During the last years, there has been growing scientific interest in their potential health benefits. In this comprehensive review, we focus on the current evidence defining the position of their dietary intake in the prevention/treatment of human chronic diseases, including prostate cancer and other types of cancer, cardiovascular diseases, diabetes mellitus and neurodegenerative diseases such as Alzheimer's and Parkinson's disease; we also discuss their ability to modulate multiple signalling transduction pathways involved in the pathophysiology of these diseases. Despite the fact that data regarding the biological functions of polyphenols can be considered exhaustive, evidence is still inadequate to support clear beneficial effects on human chronic diseases. Currently, most data suggest that a combination of phytochemicals rather than any single polyphenol is responsible for health benefit. More studies investigating the role of polyphenols in the prevention of chronic human diseases are needed, especially for evaluating factors such as gender, age, genotype, metabolism and bioavailability.
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http://dx.doi.org/10.1016/j.fct.2017.10.023DOI Listing
December 2017

Oral toxicity study of certain plant extracts containing pyrrolizidine alkaloids.

Rom J Morphol Embryol 2016 ;57(3):1017-1023

Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, Romania;

Pyrrolizidine alkaloids (PAs) are a class of toxic compounds which are found in plants. Poisoning caused by these toxins is associated with acute and chronic liver damage. Tussilago farfara (coltsfoot), Petasites hybridus (common butterbur), Senecio vernalis (eastern groundsel) and Symphytum officinale (comfrey) are traditional phytotherapic species, which beside the therapeutic bioactive compounds contain PAs. The aim of the paper was to assess the safety of some dry extracts obtained from these species. For the determination of acute toxicity, Organization for Economic Cooperation and Development (OECD) Guideline No. 423 was used. For the determination of repeated dose oral toxicity, Senecionis vernalis herba and Symphyti radix extracts (250 mg÷kg) were administrated, by gavage, for 28 days, and their effects on animal weight, liver and biliary functions, hepatic tissue and oxidative stress were investigated. After the acute toxicity testing, the dry extracts were placed in the GHS Category V (LD50>5000 mg÷kg, p.o.). For the subacute toxicity testing, no death or any signs of toxicity were observed. Also, no significant differences in biochemical parameters were observed between control and treated groups. The observed histopathological lesions were non-specific and were not consistent with the data reported in the literature for PAs exposure. In conclusion, the administration for 28 days, of the tested extracts, in a dose which correspond to a PAs concentration over the limits imposed in some countries, produced no hepatic and biliary toxic effects. Further studies, extended over a longer period of time, are needed in order to determine the safety of plant extracts containing PAs.
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May 2017

Pharmacotoxicological screening on new derivatives of beta-phenylethylamine, potential agonists of beta3-adrenergic receptors.

Rom J Morphol Embryol 2016 ;57(3):969-978

Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, Romania;

Background And Aims: Beta3-adrenergic receptors (beta3-ARs) have been initially characterized in 1989. Afterwards, their tissue distribution was established: white and brown adipose tissue, central nervous system, myocardium (atrial and ventricular), blood vessels, smooth gastrointestinal muscles (stomach, small intestine, colon), gallbladder, urinary bladder, prostate, skeletal muscles. Non-clinical trials have demonstrated the major implication of beta3-ARs in glucose metabolism, implicitly, in insulin release, and also in obesity. Therefore, new compounds were synthesized starting from beta-phenylethylamine nucleus and substituted in various positions, for possible antidiabetic and÷or antiobesity action.

Materials And Methods: In the present research, the antidiabetic action of newly synthesized compounds was investigated on an experimental model of alloxan-induced diabetes, administered in dose of 130 mg÷kg body weight (bw), intraperitoneally (i.p.). After 14 days of treatment, glycemia and enzymes involved in homeostasis of glucose metabolism, glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase (G6Pase) and hexokinase were determined. Animals were then euthanized and histopathology examinations were performed on harvested liver, kidney, spleen and brain in order to document pathological changes induced by alloxan-induced diabetes and÷or by tested compounds.

Results And Conclusions: Glycemia in animals treated with the tested compounds decreased statistically significant for groups C2 and C3 (-42.13% and -37.2%, respectively), compared to diabetic control group. C2 was also the compound to favorably modify the dynamics of determined enzymes, together with the display of very good safety profile supported by minor, non-significant, histopathological changes.
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May 2017

Lipoprotein redox status evaluation as a marker of cardiovascular disease risk in patients with inflammatory disease.

Mol Med Rep 2017 Jan 28;15(1):256-262. Epub 2016 Nov 28.

Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, Heraklion 71003, Greece.

Patients with chronic inflammatory disorders (ID) have an increased risk of developing cardiovascular disease, and routinely determined parameters do not reveal the real metabolic status of specific subgroups, such as patients with rheumatoid arthritis (RA). In this study, in order to evaluate state of the art markers for the assessment of cardiometabolic risk, abnormalities in lipoprotein levels in patients with a low‑grade inflammatory status [diabetes mellitus (DM) subgroup] and in patients with a high systemic inflammatory burden (RA subgroup) was determined. The study group comprised patients with ID [DM (n=20) and RA (n=20)], with an aged‑matched control group (n=17). Patient serum was used to determine routine biochemical parameters and to isolate low‑density lipoprotein (LDL) and high‑density lipoprotein (HDL). The heparin‑citrate method was used for LDL precipitation and the phosphotungstic acid‑MgCl2 technique for the isolation of HDL. Further, Amplex Red and advanced oxidation protein product (AOPP) assays were applied to determine lipid peroxides and protein oxidation, respectively, while the levels of serum advanced glycation end products (AGEs) were also determined. Although the differences in the routinely determined lipidemic profile were notable between the DM and RA subgroups, markers of lipid peroxidation and of advanced protein oxidation/glycation did not differ significantly, indicating possible similar oxidative damage of serum lipoproteins. On the whole, as alterations in lipoprotein functionality can occur long before any changes in routinely measured biochemical parameters are observed, more sensitive markers for the assessment of cardiovascular risk are required. As AOPPs, AGEs, oxidized LDL (oxLDL) and especially oxidized HDL (oxHDL) are affected during the early stages of inflammatory disease, and due to their known link to coronary artery disease, it would be wise to include these markers in the routine cardiovascular evaluation of patients with chronic inflammatory disease, such as those with RA.
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http://dx.doi.org/10.3892/mmr.2016.5972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355743PMC
January 2017

Structural Analysis of Sortase A Inhibitors.

Molecules 2016 Nov 22;21(11). Epub 2016 Nov 22.

Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Traian Vuia 6, Bucharest 020956, Romania.

Bacterial sortases are cysteine transpeptidases that regulate the covalent linkage of several surface protein virulence factors in Gram-positive bacteria. Virulence factors play significant roles in adhesion, invasion of host tissues, biofilm formation and immune evasion, mediating the bacterial pathogenesis and infectivity. Therefore, sortases are emerging as important targets for the design of new anti-infective agents. We employed a computational study, based on structure derived descriptors and molecular fingerprints, in order to develop simple classification methods which could allow predicting low active or high active SrtA inhibitors. Our results indicate that a highly active SrtA inhibitor has a molecular weight ranging between 180 and 600, contains one up to four nitrogen atoms, up to three oxygen atoms and under 18 hydrogen atoms. Also the hydrogen acceptor number and the molecular flexibility, as assessed by the number of rotatable bounds, have emerged as the most relevant descriptors for SrtA affinity. The Bemis-Murcko scaffolding revealed favoured scaffolds as containing at least two ring structures bonded directly or merged in a condensed cycle. This data represent a valuable tool for identifying new potent SrtA inhibitors, potential anti-virulence agents targeted against Gram-positive bacteria, including multiresistant strains.
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http://dx.doi.org/10.3390/molecules21111591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272945PMC
November 2016

Adiponectin: possible link between metabolic stress and oxidative stress in the elderly.

Aging Clin Exp Res 2017 Aug 29;29(4):621-629. Epub 2016 Sep 29.

Ana Aslan - National Institute of Gerontology and Geriatrics, 9 Caldarusani street, sector 1, PO Box 2-4, 011241, Bucharest, Romania.

Objective: The aim of this study was to evaluate the relationships between the serum levels of adiponectin and systemic oxidative stress exerted on lipids, proteins, as well as endothelial function and cardiovascular diseases (CVD) risk markers, in elderly subjects with metabolic syndrome (MS).

Methods: The serum advanced glycation and oxidation protein products, low-density lipoprotein susceptibility to oxidation (oxLDL), nitric oxide metabolic pathway products (NOx), serum lipid peroxidation, as well as total antioxidant/oxidative capacity (TAC/TOC), were analyzed in elderly subjects with MS (n = 44), compared to aged-matched control (n = 39).

Results: We pointed out significantly lower levels of adiponectin in elderly MS subjects concomitantly with significantly higher levels of oxidative stress and CVD risk markers. Significant positive correlations were found between serum adiponectin levels and HDL-cholesterol (p < 0.05) and the total cholesterol/LDL-cholesterol ratio (p < 0.01). Additionally, adiponectin levels were significantly inversely associated with insulin resistance index (HOMA-IR, r = -0.348; p < 0.05) and serum lipid peroxidation (r = -0.337; p < 0.05), and significantly positively with the antioxidant capacity (TAC, r = 0.339; p < 0.05). Conversely, adiponectin levels were significantly negatively (r = -0.310; p < 0.05) associated with serum uric acid concentration.

Conclusions: The major protective role of adiponectin versus stress related to an impaired glucose and lipid metabolism suggests that adiponectin plays a critical role in adiposity-related metabolic stress and redox homeostasis.
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http://dx.doi.org/10.1007/s40520-016-0629-zDOI Listing
August 2017

Akt inhibitors in cancer treatment: The long journey from drug discovery to clinical use (Review).

Int J Oncol 2016 Mar 24;48(3):869-85. Epub 2015 Dec 24.

Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, Heraklion 71003, Greece.

Targeted cancer therapies are used to inhibit the growth, progression, and metastasis of the tumor by interfering with specific molecular targets and are currently the focus of anticancer drug development. Protein kinase B, also known as Akt, plays a central role in many types of cancer and has been validated as a therapeutic target nearly two decades ago. This review summarizes the intracellular functions of Akt as a pivotal point of converging signaling pathways involved in cell growth, proliferation, apoptotis and neo‑angiogenesis, and focuses on the drug design strategies to develop potent anticancer agents targeting Akt. The discovery process of Akt inhibitors has evolved from adenosine triphosphate (ATP)‑competitive agents to alternative approaches employing allosteric sites in order to overcome the high degree of structural similarity between Akt isoforms in the catalytic domain, and considerable structural analogy to the AGC kinase family. This process has led to the discovery of inhibitors with greater specificity, reduced side-effects and lower toxicity. A second generation of Akt has inhibitors emerged by incorporating a chemically reactive Michael acceptor template to target the nucleophile cysteines in the catalytic activation loop. The review outlines the development of several promising drug candidates emphasizing the importance of each chemical scaffold. We explore the pipeline of Akt inhibitors and their preclinical and clinical examination status, presenting the potential clinical application of these agents as a monotherapy or in combination with ionizing radiation, other targeted therapies, or chemotherapy.
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http://dx.doi.org/10.3892/ijo.2015.3306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750533PMC
March 2016

Comparative evaluation of short-term toxicity of inorganic arsenic compounds on Artemia salina.

Rom J Morphol Embryol 2015 ;56(3):1091-6

Department of Biochemistry, Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania;

The study aimed to assess the short-term effects exerted by two inorganic arsenic species (arsenite and arsenate) on Artemia salina after 24, 48 and 72 h. The dose-lethality curves obtained indicate that the lethality induced by arsenite was higher than by arsenate. The lowest observed effect concentration for arsenite (0.5 μg/mL) is similar with the no observed effect concentration for arsenate, thus indicating that the toxicity of arsenite is higher compared with arsenate. Also, the lethal concentration 50 values confirm that arsenite induced about 1.24-fold higher toxicity than arsenate at 24 h and about three-fold higher toxicity at 48 h and 72 h of exposure. Both LC50 (lethal concentration 50) values are indicating negligible effects exhibited by arsenic at this trophic level after short-term exposure. The predicted no effect concentration in the surface aquatic compartment corresponds to 10.38 μg/L, similar to the limit imposed by Directive 98/83/EC.
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November 2016

Assessment of the potential health benefits of certain total extracts from and .

Exp Ther Med 2015 Nov 2;10(5):1681-1688. Epub 2015 Sep 2.

Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, Heraklion 71003, Greece.

A number of recent studies have illustrated the active role of food/natural components in the prevention of chronic diseases and in the improvement of the quality of life. In the present study, we aimed to obtain and characterize certain extracts from L., L. and L., focusing on their antioxidant effects . Three vegetal extracts were obtained for each plant: in water, 50% water-alcohol and in 96% ethanol. These extracts were then analyzed for their qualitative composition by high performance thin layer chromatography (HPTLC) and total phenolic content by ultraviolet-visible spectrophotometry (UV-VIS). The antioxidant activity of the extracts was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay; the effects of lipid peroxidation on the cell membrane were evaluated using Jurkat cells in two experimental models: normoglycemic and hyperglycemic medium, in order for the results to be able to be translated into clinical practice. In addition, the resistance of the extracts to acid and alkaline hydrolysis was investigated. The obtained extracts had 0.4-39 µg phenolics/mg total extract. The largest amount of phenolics was found in the extracts, while the lowest was found in the extacts. HPTLC analysis identified the main phenolic compounds in the extracts which were ferulic acid, gallic acid, caffeic acid and coumaric acid, as well as quercetin, kaempferol, apigenin, curcumin, luteolin and esculetin. The extracts had a low antioxidant efficacy, while both the and extracts had a high antioxidant activity; the products resulting from alkaline hydrolisis were significantly more efficient in scavenging DPPH radicals compared to the products resulting from acid hydrolisis. The antioxidant effects of the extracts exerted on the membranes of Jurkat cells were the most prominent under both normal and hyperglycemic conditions. The results of the present study may be translated into clinical practice and demonstrate that extracts may be effective in both the prevention of diabetes mellitus and in attenuating the development of complications associated with the disease.
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http://dx.doi.org/10.3892/etm.2015.2724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665218PMC
November 2015

Anticancer potential of selected Adans species.

Oncol Lett 2015 Sep 2;10(3):1323-1332. Epub 2015 Jul 2.

Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, Heraklion 71003, Greece.

The aim of the present study was to determine the anticancer potential of three species belonging to the genus (Polygonaceae): (, () and (). For this purpose, crude extracts were obtained and characterized for their phenolic and flavonoid total content and examined for their anticancer activity on three tumor cell lines: breast cancer (MCF7), colon carcinoma (Caco-2) and cervical cancer (HeLa) cells. The cytotoxic potential of the three species was assessed by MTT assay, cell cycle analysis and by the evaluation of mitochondrial membrane potential (MMP). The acute toxicity of the extracts was evaluated using one cell model (Vero cells, an African Green monkey kidney cell line) and two invertebrate models ( and ). The highest total phenolic and flavonoid content was found in the flower extracts. The cytotoxic effects of the extracts from and on all three cell lines were examined at concentrations ranging from 3 to 300 µg/ml. G2/M cell cycle arrest was induced by all the extracts, and a significant increase in the subG1 cell population was observed. The hydroethanolic extract from the flowers of induced cell apoptosis more rapidly than the other extracts. The MMP indicates the involvement of the mitochondria in the induction of apoptosis. A positive correlation between the total phenolic content of the extracts and the IC values against the HeLa cells was also noted. None of the extracts exhibited significantly toxic effects. Considering the antitumor potential of and , these two species may represent a good source of plant extracts with anticancer properties.
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http://dx.doi.org/10.3892/ol.2015.3453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533735PMC
September 2015

Studies regarding the protective effects exhibited by antidepressants on cell models.

Rom J Morphol Embryol 2015 ;56(2 Suppl):781-8

Department of Toxicology, Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania;

The study aimed to assess in vitro the short-term effects exerted by fluoxetine, sertraline and venlafaxine on certain physiological properties in two different study models: U937 monocytes and erythrocytes isolated from patients treated with the above-mentioned molecules. Results on U937 cell suspensions revealed the depolarization of the cell membrane induced by the three antidepressants. The maximal depolarization effect was registered after 15 minutes of cell exposure and was concentration-dependent, in a non-monotonic manner. The effect was also dependent on the tested compound, fluoxetine presenting the strongest depolarizing effect compared to sertraline and venlafaxine. The erythrocyte susceptibility to lipid peroxidation and glucose-6-phosphate dehydrogenase activity were assessed on red blood cells isolated from patients with depressive disorder. Our results revealed that antidepressant treatment induced the antioxidant defense, by decreasing erythrocyte susceptibility to lipid peroxidation and increasing glucose-6-phosphate dehydrogenase activity. The effect is more intense in the case of severe pathology and less evident in the case of moderate or minor disorder, as expressed by MADRS (Montgomery-Åsberg Depression Rating Scale) score. Our results could indicate that selected antidepressants at therapeutic concentrations, besides their known pharmacological effects, exhibit a protective effect against oxidative stress and also influence cells with immune properties.
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May 2016

Natural products-friends or foes?

Toxicol Lett 2015 Aug 14;236(3):154-67. Epub 2015 May 14.

University of Crete, Faculty of Medicine, Department of Forensic Sciences & Toxicology, Heraklion, Greece.

A trend in the general population has been observed in recent years regarding the orientation toward preventive measures in health; in this context the increased interest from the users and researchers concerning the active effect of food supplements on the health state and on longevity, is noticeable. All over the world, the consumption of natural foods and of vegetal supplements has increased spectacularly over the last 5-10 years. The decreased prevalence of cardio-vascular diseases associated with Mediterranean diet, as well as the French paradox convinced researchers to scientifically document the beneficial outcomes pointed out by traditional use of plants, and to try to develop supplements that would have the same positive effects as these noticed for diet components. The intense research dedicated to this topic revealed the fact that food supplements are linked to some problematic aspects, such as toxicological side effects when associated with classical synthetic drugs. The food supplement-drug interactions are submitted to complex issues regarding pharmacokinetic interactions leading to changes in absorption, distribution, metabolism and excretion processes with direct impact on effect and toxicological potential. The present review based on recent literature aims at discussing the food-drug interactions with direct impact on efficacy and toxicity of drugs.
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http://dx.doi.org/10.1016/j.toxlet.2015.05.009DOI Listing
August 2015

The prevalence of the red cell morphology changes in patients with type 2 diabetes mellitus.

Rom J Morphol Embryol 2015 ;56(1):183-9

Department of Pathologic Physiology, University of Medicine and Pharmacy of Craiova, Romania;

Previous studies have shown that hematological alterations are a common finding in patients with diabetes. The aim of our study was to estimate the prevalence of the red cell morphology changes in diabetic patients and their correlation with markers of glycemic control. Thirty patients with type 2 diabetes mellitus were recruited for this study. Patient demographics, relevant concomitant illnesses and medical history were recorded. Anthropometric, biochemical parameters (fasting plasma glucose - FPG, glycated hemoglobin - HbA1c, glomerular filtration rate - GFR) and morphology of blood smear were assessed. Results were compared with the same measurements in 30 subjects without diabetes mellitus. The groups were similar in terms of age and gender but there were statistically significant differences for the recorded parameters in patients of study group and control subjects. Regarding the assessment of FPG, in the study group were recorded averages of 217.70±73.20 mg÷dL compared with controls that compared with controls that had a blood glucose value of 90.03±6.59 mg÷dL. In the study group, mean HbA1c was 7.95±1.99%. For the control group, the mean value of HbA1c was 5.65±0.32%. In the study group, GFR ranged between 47.70 and 118.90 mL÷min.÷1.73 m². For the control group, GFR values were between 88.00 and 130.00 mL÷min.÷1.73 m². In the analysis of blood cytology for the study group, there were changes in the smear type hypochromia, anisocytosis and poikilocyosis (20 patients - 66.66%). In terms of red cell morphology, changes were recorded anulocytes type, red cells in "mark to the target fired" (codocytes), bream (leptocytes), schizocytes, and red cells in "drop" (dacryocytes). We observed a high prevalence of the red cell morphology changes in diabetic patients compared with non-diabetic subjects. Our findings suggest the need of screening for routine hematological tests in type 2 diabetes mellitus.
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April 2016

In vitro effects of prolonged exposure to quercetin and epigallocatechin gallate of the peripheral blood mononuclear cell membrane.

Cell Mol Biol Lett 2014 Dec 13;19(4):542-60. Epub 2014 Oct 13.

Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia St., 020956, Bucharest, Romania.

The study aimed to assess biophysical changes that take place in the peripheral blood mononuclear cell (PBMC) membranes when exposed in vitro to 10 μM quercetin or epigallocatechin gallate (EGCG) for 24 and 48 h. PBMCs isolated from hypercholesterolemia patients were compared to those from normocholesterolemia subjects. The membrane fluidity and transmembrane potential were evaluated and the results were correlated with biochemical parameters relevant to oxidative stress, assessed in the patients' plasma. The baseline value of PBMC membrane anisotropy for the hypercholesterolemia patients was lower than that of the control group. These results correlated with the plasma levels of advanced glycation end products, which were significantly higher in the hypercholesterolemia group, and the total plasma antioxidant status, which was significantly higher in normocholesterolemia subjects. In the case of normocholesterolemia cells in vitro, polyphenols induced a decrease in membrane anisotropy (7.25-11.88% at 24 h, 1.82-2.26% at 48 h) and a hyperpolarizing effect (8.30-8.90% at 24 h and 4.58-13.00% at 48 h). The same effect was induced in hypercholesterolemia cells, but only after 48 h exposure to the polyphenols: the decrease in membrane anisotropy was 5.70% for quercetin and 2.33% for EGCG. After 48 h of in vitro incubation with the polyphenols, PBMCs isolated from hypercholesterolemia patients exhibited the effects that had been registered in cells from normocholesterolemia subjects after 24 h exposure. These results outlined the beneficial action of the studied polyphenols, quercetin and EGCG, as dietary supplements in normocholesterolemia and hypercholesterolemia patients.
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http://dx.doi.org/10.2478/s11658-014-0211-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275756PMC
December 2014